Synthesis and characterization of dithioethers, and their RuII and RuIII complexes

Article abstract of DOI:10.1016/j.ica.2019.04.056

The syntheses of nine, new dithioethers of the type RS(CH₂)_xSR, where x = 2 or 3 and R is an alkyl chain, as well as the known x = 2, R = phenyl or cyclohexyl compounds, are reported. The known dithioethers react with RuCl₃·3H₂O to form trans-RuCl₂(dithioether)₂ complexes 1 (R = Ph) and 2 (R = C₆H₁₁), whereas from the other dithioethers RuCl₂[RS(CH₂)_xSR]₂(μ-Cl)₂ complexes have been isolated, where x = 3, and R = Et (complex 3), ⁿPr (complex 4), ⁿBu (complex 5), and R = ⁿpentyl (complex 6). The complexes are well characterized, including X-ray structures for complexes 1–4. The interest in these compounds stems from oxidation of the dithioethers to the corresponding disulfoxides and their Ru complexes.

Full text of DOI:10.1016/j.ica.2019.04.056

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Synthesis and characterization of dithioethers, and their RuII and RuIII complexes
Elizabeth L.S. Cheu, Donald T.T. Yapp, Brian O. Patrick, Brian R. James
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https://doi.org/10.1016/j.ica.2019.04.056
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Please cite this article as: E.L.S. Cheu, D.T.T. Yapp, B.O. Patrick, B.R. James, Synthesis and characterization of
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2019.04.056
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Synthesis and characterization of dithioethers, and their RuII and RuIII
complexes
Elizabeth L.S. Cheu,a,b Donald T. T. Yapp,a,b Brian O Patrick,a Brian R. James a,*
a
Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
b Advanced Therapeutics, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada
ABSTRACT
The syntheses of nine, new dithioethers of the type RS(CH2)xSR, where x = 2 or 3 and R is an alkyl
chain, as well as the known x = 2, R = phenyl or cyclohexyl compounds, are reported. The known
dithioethers react with RuCl3·3H2O to form trans-RuCl2(dithioether)2 complexes 1 (R = Ph) and
2 (R = C6H11), whereas from the other dithioethers RuCl2[RS(CH2)xSR]2(-Cl)2 complexes have
n
n
been isolated, where x = 3, and R = Et (complex 3), Pr (complex 4), Bu (complex 5), and R =
npentyl (complex 6). The complexes are well characterized, including X-ray structures for
complexes 1 to 4. The interest in these compounds stems from oxidation of the dithioethers to the
corresponding disulfoxides and their Ru complexes.
Keywords: dithioethers; Ru(II and III) complexes; X-ray structures
Received………..2019. Accepted…….
_______
*Corresponding author.
E-mail address: brj@chem.ubc.ca (B.R. James).
1

1. Introduction
Our long-time interest in Ru-dithioether complexes stems from use of platinum metal thioethers
as hydrogenation catalysts [1], and Chatt et al. noted this in a 1971 paper on syntheses of a wide
range of RuII- and RuIII-chloro/bromo complexes containing organic mono-, di- , or tri-sulfides
(thioethers); however, no crystal structures were given [2]. Our current interest in Ru-dithioether
species was based on the finding that some could be converted to the corresponding sulfoxide
complexes by O2-oxidation [3] or an oxidant such as dimethyldioxirane or m-CPBA [4]. A specific
aim of synthesizing RuCl2(dithioether)2 complexes was to determine the cis- or trans-geometry,
and then oxidize the coordinated dithioethers to the Ru-disulfoxides to investigate if this geometry
was retained. Stereochemistry within the coordinated sulfoxides and disulfoxides is also of
significant interest, particularly within ruthenium complexes considering: (a) the anti-cancer and
other biological activities such as hypoxic agents, as found for RuCl2(DMSO)4, and other Ru-
sulfoxide/disulfoxide complexes [5,6]; and (b) the radiosensitizing activity of such species when
containing also a nitroimidazole co-ligand [6].
This current paper reports on the synthesis of 9 new and 2 known dithioethers, and their
reactions with the commercially available RuCl3·3H2O. Table 1 shows the commonly used names
and abbreviations of the dithioethers.
Findings on the corresponding sulfoxides and related ones, and their interaction with
RuCl3·3H2O, will be reported later, together with their in vitro studies such as cell accumulation
and toxicity, and DNA binding [7].
2

Table 1
Names and, when appropriate, abbreviations used for the RS(CH2)xSR dithioethers; the alternative
name refers to replacement of a CH2 by a S-atom in linear CH2-chain groups.
x
R
Name
Abbreviation Alternative name
2
n-butyl
n-hexyl
phenyl
1,2-bis(butylthio)ethane
1,2-bis(hexylthio)ethane
1,2-bis(phenylthiol)ethane
BBTE
BHTE
BPhTE
5,8-dithiadodecane
2
2
2
2
3
3
3
3
3
3
7,10-dithiahexadecane
cyclohexyl 1,2-bis(cyclohexylthio)ethane BCyTE
n-pentyl
ethyl
1,2-bis(pentylthio)ethane
1,3-bis(ethylthio)propane
1,3-bis(propylthio)propane
BPeTE 6,9-dithiatetradecane
BETP
BPTP
3,7-dithianonane
n-propyl
t-butyl
n-butyl
n-pentyl
phenyl
4,8-dithiaunadecane
2,8-dimethyl-3,7-dithianonane BiPTP
1,3-bis(butylthio)propane
1,3-bis(pentylthio)propane
1,3-bis(phenylthio)propane
BBTP
5,9-dithiatridecane
BPeTP 6,10-dithiapentadecane
BPhTP
2. Experimental section
2.1. General
1,2-Dibromoethane was a Fisher Scientific product, and 1,3-dibromopropane was obtained
from MCB, while ethane-, propane-, butane-, pentane-, hexane- and cyclohexyl-thiols, were
Aldrich products; benzenethiol was an Eastman product. Other common commercial chemicals
were purchased from Fisher Scientific, and used as provided. Syntheses of the dithioethers are
described in Section 2.2.
RuCl3·3H2O was donated by Colonial Metals Inc. All common solvents used were at least of
reagent grade; CDCl3 was purchased from MSD Isotopes. Alumina (neutral, Brockman activity I)
was purchased from Fisher chemicals. All samples (products and solvents) were stored in air, and
all syntheses and measurements were carried out in air unless otherwise noted. Syntheses of the
RuII and Ru2III complexes are described in Sections 2.3 and 2.4, respectively. Elemental analyses
(EA) were performed in the UBC chemistry department on a Carlo Erba 1106 instrument, with
data having an accuracy of ±0.3%.
3

NMR spectra were obtained in CDCl3 solutions of the compounds using a Bruker AC-200E
(200 MHz) instrument. Proton shifts are given with reference to the residual CHCl3 solvent peak
( 7.24) as the internal standard, relative to TMS. The 1H-NMR shifts are reported as indicated by
s = singlet; t = triplet; q = quartet; quin = quintet; sext = sextet; m = multiplet, br = broad. UV-
visible data were measured on a Hewlett-Packard 8452A diode array spectrophotometer, max
being given in nm, followed by an extinction coefficient given as log . Mass spectra were
measured using +LSIMS on a KRATOS Concept IIHQ.
Determination of the eff and number of unpaired electrons for selected paramagnetic RuIII
complexes was performed at r.t. using a Johnson-Matthey Mk1 Magnetic Susceptibility Balance.
◦
Conductivity measurements were attempted at room temperature (r.t. ~20 C) at ~10-3
M
concentrations using a Thomas Serfass conductivity bridge, and a cell from Yellow Springs
Instrument Company, the cell constant being determined as 1.016.
2.2. Synthesis of Dithioethers
2.2.1. 3,7-Dithianonane (BETP)
Ethanethiol (30 mL, 400 mmol) was added dropwise to a saturated solution (50 mL) of NaOH
in MeOH cooled in a dry-ice/acetone bath; the mixture was then stirred at 70 ºC for 1 h, and then
cooled again prior to dropwise addition of 1,3-dibromopropane (20.6 mL, 200 mmol) with stirring.
After being warmed at 70 ºC for 1 h, the solution was poured into H2O (100 mL), and the oily,
immiscible dithioether layer was collected. The aqueous layer was extracted three times with Et2O
(40 mL) portions, the organic residues being combined; the Et2O was removed by rotary
evaporation, and the oily product was dried over MgSO4. Yield 21 g (64 %). Anal. Calc.(found)
for C7H16S2: C, 51.17 (51.0); H, 9.81 (9.8). 1H-NMR:  2.60 (m, 8H, CH2SCH2), 1.85 (quin, 2H,
CH2CH2CH2), 1.25 (t, 6H, CH3). Mass spectrum: 164 [M]+, 135 [M-C2H5]+.
2.2.2. 4,8-Dithiaunadecane (BPTP)
As above, but using 1-propanethiol (30 mL, 330 mmol) and 1,3-dibromopropane (16.8 mL, 165
mmol). Yield 28 g (88 %). Anal. Calc. (found) for C9H20S2: C, 56.19 (57.7); H, 10.48 (10.8). 1H-
NMR:  2.60 (t, 4H, CH2CH2CH2), 2.50 (t, 4H, CH2CH2CH3), 1.85 (quin, 2H, CH2CH2CH2), 1.60
(sext, 4H, CH2CH2CH3), 1.02 (t, 6H, CH3). Mass spectrum:192 [M]+, 149 [M-C3H7]+.
4

2.2.3. 2,8-Dimethyl-3,7-dithianonane (BiPTP)
As above, but using 2-propanethiol (40 mL, 430 mmol) and 1,3-dibromopropane (21.9 mL, 210
mmol). Yield 32 g (80 %). Anal. Calc. (found) for C9H20S2: C, 56.19 (55.32); H, 10.48 (10.39).
1H-NMR:  2.90 (m, 2H, (CH3)2CHS), 2.60 (t, 4H, CH2CH2CH2), 1.85 (quin), 2H, CH2CH2CH2),
1.30 (d, 12H, SCH(CH3)2). Mass spectrum: 193 [M]+.
2.2.4. 5,9-Dithiatridecane (BBTP)
As above, but using butanethiol (40 mL, 370 mmol) and 1,3-dibromopropane (18.9 mL, 187
mmol). Yield 36 g (87 %). Anal. Calc. (found) for C11H24S2: C, 59.94 (59.6); H, 10.97 (11.1). 1H-
NMR:  2.60 (m, 8H, CH2SCH2), 1.85 (quin, 2H, CH2CH2CH2), 1.56 (quin, 4H, CH2CH2CH3),
1.42 (st, 4H, CH2CH3), 0.92 (t, 6H, CH3). Mass spectrum: 220 [M]+, 163 [M-C4H9]+.
2.2.5. 6,10-Dithiapentadecane (BPeTP)
As above, but using pentanethiol (23.8 mL, 192 mmol) and 1,3-dibromopropane (9.7 mL, 96
mmol). Yield 21 g (88 %). Anal. Calc. (found) for C13H28S2: C, 62.84 (60.6); H, 11.36 (11.1). 1H-
NMR:  2.56 (m, 8H, CH2SCH2), 1.85 (quin, 2H, CH2CH2CH2), 1.56 (quin, 4H,
CH2CH2CH2CH3), 1.35 (m, 8H, CH2CH2CH3), 0.92 (t, 6H, CH3). Mass spectrum: 248 [M]+, 177
[M-C5H11]+.
2.2.6. 1,3-Bis(phenylthio)propane (BPhTP)
As above, but using benzenethiol (50 mL, 487 mmol) and 1,3-dibromopropane (24.7 mL, 244
1
mmol). Yield 47 g (74 %). Anal. Calc. (found) for C15H16S2: C, 69.18 (68.3); H, 6.19 (6.3). H-
NMR:  7.55 (m, 10H, C6H5), 2.93 (m, 4H, CH2CH2CH2 ), 2.10 (m, 2H, CH2CH2CH2). Mass
spectrum: 260 [M]+. The 1H NMR data compare well with literature data [9].
2.2.7. 5,8-Dithiadodecane (BBTE)
As above, but using butanethiol (13 mL, 120 mmol) and 1,2-dibromoethane (5.3 mL, 61 mmol).
Yield 14.5 g (58 %). Anal. Calc. (found) for C10H22S2: C, 58.19 (58.4); H, 10.74 (10.8). 1H-NMR:
 2.73 (t, 4H, SCH2CH2S), 2.55 (t, 4H, CH2S), 1.45 (m, 8H, CH2CH2CH3), 0.90 (t, 6H, CH3).
Mass spectrum: 206 [M]+, 149 [M-C4H9]+.
5

2.2.8. 6,9-Dithiatetradecane (BPeTE)
As above, but using pentanethiol (9.8 mL, 80 mmol) and 1,2-dibromoethane (3.4 mL, 40
mmol). Yield 6.1 g (65 %). Anal. Calc. (found) for C12H26S2: C, 61.48 (61.1); H, 11.18 (11.0).
1H-NMR:  2.75 (t, 4H, SCH2CH2S), 2.55 (t, 4H, CH2S), 1.60 (quin, 4H, CH2CH2CH2CH3), 1.35
(m, 8H, CH2CH2CH3), 0.92 (t, 6H, CH3). Mass spectrum: 234 [M]+.
2.2.9. 7,10-Dithiahexadecane (BHTE)
As above, but using hexanethiol (40 mL, 280 mmol) and 1,2-dibromoethane (12.2 mL, 142
mmol). Yield 25 g (67 %). Anal. Calc. (found) for C14H30S2: C, 64.06 (63.9); H, 11.52 (11.4). 1H-
NMR: 2.75 (t, 4H, SCH2CH2S), 2.55 (t, 4H, CH2S), 1.55 (quin, 4H, CH2CH2CH2CH2CH3), 1.30
(m, 12H, CH2CH2CH2CH3), 0.95 (t, 6H, CH3). Mass spectrum: 262 [M]+.
2.2.10. 1,2-Bis(phenylthio)ethane (BPhTE)
As above, but using benzenethiol (50 mL, 487 mmol) and 1,2-dibromoethane (21 mL, 240
mmol). However, the aqueous layer was this time extracted three times with CHCl3 (40 mL)
portions and, after the organic residues were combined, the CHCl3 was removed by evaporation.
The white solid obtained was then recrystallized using CH2Cl2 (7 mL) and Et2O (100 mL). Yield
39 g (65 %). Anal. Calc. (found) for C14H14S2: C, 68.25 (68.2); H, 5.73 (5.7). 1H-NMR:  7.15 (m,
10H, C6H5), 3.10 (t, 4H, CH2CH2). The 1H NMR data agree well with literature values [8,9].
2.2.11. 1,2-Bis(cyclohexylthio)ethane (BCyTE)
As above, but using cyclohexylthiol (50 mL, 400 mmol) and 1,2-dibromoethane
(17.6 mL, 204 mmol). Yield 23.7 g (45 %). Anal. Calc. (found) for
C3 C2
C
C1 S CH
2
(
)
C14H26S2: C, 65.06 (64.9); H, 10.14 (10.0).1H-NMR:  2.70 (t, 4H,
CH2CH2), 1.95, 1.75 (m 4H each, H2), 1.58 (m, 2H, H1), 1.29 (m, 12H,
4
2
C3 C2
H3,4) [H1-4 define the bonded C-atom number as shown]. Mass spectrum: 258 [M]+.
6

2.3. Synthesis of Mononuclear Ru(II) Dithioether Complexes
2.3.1. Trans-RuCl2(BCyTE)22H2O (1)
Conc. HCl (100 L) was added to a solution of RuCl3·3H2O (100 mg, 0.4 mmol) in EtOH (30
mL), and the mixture was refluxed for 5 h. 1,2-Bis(cyclohexylthio)ethane (BCyTE, 198 mg, 0.8
mmol) was added and the mixture was refluxed for a further 6 h. The resulting red precipitate was
collected by filtration and dried in vacuo. Elemental analysis was performed on the isolated
precipitate. Yield 223 mg (81 %). Anal. Calc. (found) for C28H52Cl2S4Ru·2H2O: C, 46.39 (46.82);
H, 7.78 (7.43). X-ray quality crystals were grown by recrystallization of the complex from
DMF/CH2Cl2 (500 L/2 mL) and were found to contain 2 CH2Cl2 solvates per molecule. The 1H-
NMR spectrum is a complex pattern of peaks at  1.20-3.35; attempts to assign the spectrum using
13C, 2D-COSY and 1H decoupling experiments were unsuccessful. UV-Vis (CH2Cl2) 438 (3.55),
400 (3.53), 280 (3.74), 236 (4.31).
2.3.2. Trans-RuCl2(BPhTE)2 (2)
The synthesis of the red complex was as described above, but using 1,2-bis(phenylthio)ethane
(BPhTE, 188 mg, 0.8 mmol). The product was then dissolved in minimum CH2Cl2 and purified by
column chromatography using neutral alumina with CH2Cl2 as eluant, this being removed by
rotary evaporation. Yield 184 mg (73 %). Anal. Calc. (found) for C28H28Cl2RuS4: C, 50.59 (50.82);
H, 4.24 (4.11). X-ray quality crystals were formed by evaporation of a DMF solution of the
complex. 1H-NMR:  7.65 (br s, 8H, o-C6H5), 7.28 (br s, 4H, p-C6H5), 7.12 (br s, 8H, m-C6H5),
3.07 (br s, 8H, CH2CH2). UV-Vis (CH2Cl2) 410 (3.50), 298 (4.55), 268 (4.54).
2.4. Synthesis of Dinuclear Ru2III Dithioether Complexes
2.4.1. [RuCl2(BETP)]2(-Cl)2 (3)
Conc. HCl (500 L) was added to a solution of RuCl3·3H2O (500 mg, 2 mmol) in EtOH (30
mL), and the mixture was refluxed for 5 h. BETP 600 mg, 4 mmol) was then added and the mixture
was refluxed for a further 6 h. The resulting dark-brown solution was then reduced in volume to
an oil, to which added acetone (25 mL) gave a purple-brown precipitate. X-ray quality crystals
were formed by slow evaporation of a solution of the precipitate in CH2Cl2. Yield 178 mg (24 %).
7

Anal. Calc. (found) for C7H16Cl3RuS2: C, 22.62 (22.4); H, 4.34 (4.3). UV-Vis (CH2Cl2) 454 (3.42),
376 (3.49), 268 (4.53). eff = 3.8  0.1 B. M.
2.4.2. [RuCl2(BPTP)]2(-Cl)2 (4)
The procedure used was as described above in Section 2.4.1. but using RuCl3·3H2O (100 mg,
0.4 mmol) and BPTP (147 mg, 0.8 mmol); only 15 mL of acetone were added. X-ray crystals were
again obtained from a CH2Cl2 solution of the precipitate. Yield 83 mg (52 %). Anal. Calc. (found)
for C9H20Cl3RuS2: C, 27.04 (27.5); H, 5.04 (5.1). UV-Vis (CH2Cl2) 448 (2.62), 374 (2.61), 252
(3.44). eff = 3.0  0.1 B. M.
2.4.3.[RuCl2(BBTP)]2(-Cl)2 (5)
Again the same procedure was used, but with RuCl3·3H2O (100 mg, 0.4 mmol), 5,9-BBTP (160
mg, 0.8 mmol), and 15 mL of acetone. Yield 43 mg (25 %). Anal. Calc. (found) for C11H24Cl3RuS2:
C, 30.88 (30.7); H, 5.65 (5.5). UV-Vis (CH2Cl2) 454 (3.51), 376 (3.57), 268 (4.68). eff = 3.2 
0.1 B. M.
2.4.4. [RuCl2(BPeTP)]2(-Cl)2 (6)
The above method was used with RuCl3·3H2O (100 mg, 0.4 mmol), BPeTP (190 mg, 0.8 mmol)
and a 15 mL addition of acetone. Yield 100 mg (55 %). Anal. Calc. (found) for C13H28Cl3RuS2: C,
34.25 (34.3); H, 6.19 (6.3). UV-Vis (CH2Cl2) 434 (3.41), 396 (3.45), 266 (4.86), 216 (4.83). eff
= 3.4  0.1 B. M.
2.5. X-ray crystallography
The data for the four structures were collected on a Rigaku AFC7/ADSC CCD diffractometer
with graphite-monochromated Mo-Kα radiation. All crystals were mounted on glass fibers with
oil and data were collected at -93 °C. Data for complexes 1, 2, and 4 were each collected to a
maximum 2θ of 60.1°, while data for complex 3 were collected to 63.6°. The structures were each
solved using Intrinsic Phasing [10], and refined using Shelxl-2018 [11]. Complexes 1, 3, and 4
each crystallize with one half-molecule in the asymmetric unit, related to the other by inversion
symmetry; complex 2 crystallizes with one complete molecule in the asymmetric unit. Complexes
1 and 4 each crystallize with one molecule of solvent CH2Cl2 in the asymmetric unit. All non-
8

hydrogen atoms were refined anisotropically; H-atom positions were calculated geometrically and
refined using a riding model. The ORTEP plots for complexes 1-4 are shown in Figs. 1, 2, 4 and
5, respectively, and selected bond lengths and angles are given in Tables 2 and 3. Full experimental
parameters and details of the structures are given in CIF format in the Supplementary Information.
3. Results and discussion
3.1. Dithioethers
The RS(CH2)nSR dithioethers, where n =2 or 3, and R = alkyl, cyclohexyl or phenyl, were
prepared by the reported methodology [2,8,9] of reacting an appropriate thiol with 1,2-
dibromoethane or 1,3-dibromopropane in MeOH containing NaOH, the basic solution neutralising
the HBr co-product. Different solvents and bases, including use of elemental sodium, have been
used by others [8]. All the thioethers are new, except 1,2 bis(phenylthiol)ethane) (BPhTE) and 1,3-
bis(phenylthiol)propane) (BPhTP) and, except for the latter, are all hygroscopic oils, whose
elemental analyses were not always satisfactory. The oxidations of all the above dithioethers to the
corresponding disulfoxide will be reported later, together with their reactions with various Ru
precursors [7].
3.2. Dithioether complexes of Ru
Syntheses of RuX3(thioether)3 complexes (thioether = DMS or TMS; X = Cl or Br) by reactions
of RuCl33H2O with DMSO or TMSO in the presence of HCl were reported in 1990 by our group
[12], in which thioether formation was attributed to redox processes involving RuIII and the
sulfoxide, as shown in equations 1 and 2. A related procedure, but using higher temperatures (130-
140 vs. 70-80 C), produces the ionic trans-complexes, [(DMSO)2H]+[RuCl4(DMSO)2]- and
[(TMSO)H]+[RuCl4(TMSO)2]-, where TMSO = tetramethylenesulfoxide [12,13].
2RuIII + DMSO + H2O  2RuII + DMS(O)2 + 2H+
2RuII + R2SO + 2H+ 2RuIII + R2S + H2O
(1)
(2)
The RuIII reduction, and oxidation of DMSO to the sulfone (eqn.1), were established in 1991
by the reaction of mer-RuCl3(DMSO)3 (in DMSO under Ar) to trans-RuCl2(DMSO)4 [13a];
evidence for equilibrium reaction (eqn.2) has also been presented for a system with R = Bu [14].
9

Complications are possible if the sulfoxides are not purified: e.g. DMS impurity in DMSO can
reduce RuIII to RuII [12b], and also of significance is that commercial RuCl33H2O is a mixture of
RuIII and RuIV species, the latter likely being a hydroxo species [15]. It is not surprising that the
redox aspects of syntheses involving the trichloride and thiol or dithiols (or the corresponding
sulfoxides) are not well understood.
Reported in 1971 is that RuCl3·3H2O reacts with mono-(S), di-(SS), or tri-organic sulfides
(SSS) to give, respectively, the complexes mer-[RuCl3S3], [{RuCl3(SS)1.5}n], trans-[RuCl2(SS)2],
or [RuCl3(SSS)] [2]. The [{RuCl3(RSCH2CH2SR)1.5}n] complexes (R = Me, Et, Pr or Ph) were too
insoluble for molecular weight determination, but were thought to be at least dinuclear with one
chelated and one bridging disulphide ligand; unfortunately there were no crystal structures
reported in this publication [2]. The isolation of the by-product trans-RuCl2(BPhTE)2 in this 1971
paper was rationalized by suggesting that this diphenyldithioether was a stronger reducing agent
than the R = Me, Et or Pr analogues [2]; however, our studies show that reactions of the
dicyclohexyl- or diphenyl-dithioether with RuCl33H2O result in isolation of both trans-
RuCl2(BCyTE)2 (1) and trans-RuCl2(BPhTE)2 (2), implying that such a conclusion is not valid in
a general sense. Nevertheless, the isolation of the dinuclear RuIII complexes 3 to 6, all with dialkyl
groups, tends to support the suggestion; presumably the bulky cyclohexyl group could be a factor.
Related to this apparently complicated redox chemistry is that the dialkyl-dithioethers listed in
Section 2.2. are converted to the corresponding sulfoxides by acid-catalyzed oxidation using
DMSO [7], whereas the diarylsulfoxides were synthesized by H2O2 oxidation of the corresponding
diarylsulfides by a reported method [16]. Redox studies on these Ru systems are needed to help
clarify the synthetic data. Our studies on the Ru complexes of diaryl- and dialkyl-sulfoxides [7]
will be reported elsewhere.
Worth mentioning is that there are complexes of the type cis-MX2(BBTE), where M = Pd and
Pt, X = halide, and BBTE = 1,2-bis(benzylthio)ethane) [17]; [RhCl3(PhSCH2SPh)3],
[IrCl3(PhSCH2SPh)3] and RuCl3(PhSCH2SPh)2EtOH have also been reported [18]. None of these
complexes was characterized crystallographically [17,18], but there is a structure of
Rh2Cl2(CO)2[bis(ethylthio)methane]2 [19].
In summary, our studies reveal that reactions of BPhTE and BCyTE with RuCl3·3H2O give
mononuclear trans-RuCl2(SS)2 complexes (1 and 2, Section 2.3), whereas the longer chain
10

III
dithioethers BETP, BPTP, BBTP, and BPeTP (Table 1) give the dinuclear Ru2 complexes
[RuCl2(SS)]2(-Cl)2, (3-6, Section 2.4). Again, the details of the redox chemistry remain unclear.
3.2.1. Mononuclear Ru(II) dithioether complexes: trans-RuCl2(BCyTE)2 (1) and trans-
RuCl2(BPhTE)2(2)
The BCyTE complex (1) was first isolated as a dihydrate, but recrystallization from a
DMF/CH2Cl2 solution gave crystals containing 2 CH2Cl2 solvates per molecule. The ORTEP
diagram of the centrosymmetric structure is shown in Fig. 1; Fig. S1 shows the unit cell with the
solvates. Selected bond lengths and angles are given in Table 2; there are no significant H-bonding
interactions with the CH2Cl2 molecules. The Ru-Cl bond lengths of 2.43 Å are essentially the same
as those found in the corresponding disulfoxide complex cis-RuCl2(BCySE)2, where BCySE =
1,2-bis(cyclohexylsulfinyl)ethane [7], implying that the trans influence of this sulfoxide moiety
and Cl- are similar; the Ru-S bond lengths (2.36 Å) for the dithioether complex are about 0.03 Å
longer than those of the sulfoxide complex [7]. The 1H NMR spectrum of 1 in CDCl3 is a broad
complex pattern that could not be assigned by using 13C, 2D-COSY, or 1H decoupling experiments.
No conductivity was observed for the trans-bis(dithioether) complexes in CH2Cl2 solution,
indicating no loss of chloride, and the broad signals likely result from the rotation of the cyclohexyl
rings.
11

Fig. 1. An ORTEP drawing of trans-RuCl2(BCyTE)2 (1) with 50 % probability shown; H-atoms
are omitted for clarity. The none-interacting CH2Cl2 molecules are not shown, but are included in
the unit cell structure (Fig. S1).
12

Fig. 2. An ORTEP drawing of trans-RuCl2(BPhTE)2 (2) with 50 % probability thermal ellipsoids
shown; H-atoms are omitted for clarity.
13

Table 2. Selected bond lengths (Å) and angles (º) for trans-RuCl2(BCyTE)22CH2Cl2 (1) and
trans-RuCl2(BPhTE)2 (2).
Bond or angle
trans-RuCl2(BPhTE)2 [2]
2.4232(11), 2.4251(11)
trans-RuCl2(BCyTE)22CH2Cl2 [1]
2.4268(9)
Ru-Cl
Ru-S
2.3627(10), 2.3643(9)
1.814(3)-1.838(3)
84.12(3)-95.88(3)
180.0
2.3424(10), 2.3591(10)
1.810(4)-1.830(4),a 1.782(4)-1.797(4)b
83.72(4)-98.07(4)
C-S
cis angles
trans angles
C-S-C
167.61(3)-178.11(3)
97.76(12), 104.23(12)
110.38(16), 112.78(18)
105.76(17)-112.83(18)
101.47(9), 104.04(9)
110.98(9), 117.55(9)
87.22(4); 180.0
98.28(17)-102.37(17)
S-C-Ca
S-C-Cb
Ru-S-Ca
Ru-S-Cb
S-Ru-Sc
107.0(3)-108.6(3)
115.9(3)-123.6(3)
102.62(13)-104.21(13)
116.97(12)-121.58(13)
85.99(4), 85.30(4) ; 167.61(3), 167.67(3)
a Backbone (CH2)2 atoms. b C of Cy or Ph substituents. c Data given as cis ; trans.
The X-ray structure of trans-RuCl2(BPhTE)2 (2) (Fig. 2, Table 2) confirms the geometry
previously suggested from IR data [2]. All the bond lengths are within 0.02 Å of those of complex
1, except for the C(Ph)-S bond that is ~0.06 Å shorter than the C(Et-S) bond; the major difference
in the corresponding bond angles of complexes 1 and 2 is in the S-C-C angles, where the carbon
atoms are those of the phenyl- or cyclohexyl-groups: the angle in 1 is ~11◦ larger. The cis S-Ru-S
angles in 1 and 2 are all in the 85.30 - 87.22 degree range; the trans S-Ru-S angles in 1 are 180.0◦,
and those in 2 are both ~167.6◦.
To the best of our knowledge, no structurally characterized Ru (chloro)dithioether complexes
(either of RuII or RuIII) have been reported previously. There are cationic RuII complexes with
BPhTE, where the S-atoms are trans to phenanthroline N-atoms, and the Ru-S bond lengths are
2.30-2.40 Å [20], in the same range as those of complexes 1 and 2. Similar values are seen in many
Ru-monosulfide complexes with various co-ligands [21].
1
The H NMR spectrum in CDCl3 of the free ligand BPhTE shows a singlet at  3.10 for the
CH2CH2 protons and a  7.15 multiplet for the phenyl protons. In complex 2, shifts at  7.65, 7.28
14

and 7.12, are assigned to the o-, p- and m-protons, respectively, and are based on the resonance
structures shown in Fig. 3; these show that the S-atom removes electron density from the o- and
p-positions and results in downfield shifts of these signals, while the m-protons are not directly
affected. Of interest, the synthesis of 2 used RuCl3٠3H2O and BPhTE, with EtOH as solvent in the
presence of HCl (yield 73%), whereas that ‘same’ method reported by Chatt et al. used a solution
in non-acidified 2-methoxyethanol (yield 65%) [2]. The difference in the synthetic methods could
even result from a different source of the ruthenium precursor; this was not given in ref. 2.
R
R
-
R
-
S
S
S
+
+
Fig. 3. Resonance structures of a phenyl thioether.
Mentioned in the Introduction is the report that RuII thioether complexes can be converted
with dimethyldioxirane to the corresponding sulfoxide complexes; an example given was
[RuCp(chiraphos)(SR/R')]PF6, where R/R' = Me/Ph, Me/iPr, Me/Bz, Et/Bz or Me/Cy [4a]. This
suggested a possible oxidation route of 1 and 2 to the corresponding Ru disulfoxide complexes; an
attempt to oxidize 2 by this method, however, was unsuccessful: no SO was detected in an
isolated crude product, and no colour change of the reaction solution was observed.
III
3.2.2. Dinuclear Ru2 -dithioether complexes
Reactions of 3,7-dithianonane, 4,8-dithiaunadecane, 5,9-dithiatridecane, and 6,10-dithiapenta-
III
decane with RuCl33H2O gave, respectively, the dark purple-brown, dinuclear Ru2 complexes
[RuCl2(SS)]2(-Cl)2, where SS = BETP (3), BPTP (4), BBTP (5), and BPeTP (6). Crystal
structures of 3 and 4 (Figs. 4, 5, and Table 3) are very similar, not surprisingly since the only
difference is the S-alkyl (Et vs. Pr). Somewhat surprisingly, since the crystals were made via the
same method (from a CH2Cl2 solution), the X-ray structure of 4 shows 2 CH2Cl2 solvates whereas
3 has no solvate molecules; however, crystals of the butyl and pentyl analogues 5 and 6 could not
be isolated.
15

Differences in the corresponding bond lengths and angles in 3 and 4 (Table 2) are again small.
The terminal Ru-Cl bond lengths (trans to S) are essentially the same, and are only about 0.03 Å
longer than those trans to the μ-Cl, implying a small trans influence of S compared to the μ-Cl.
Similar relative data and implication are seen for the Ru-μ-Cl bond lengths that are trans to the S
or a terminal-Cl, where a relative difference of ~0.07 Å is seen. There are only minor
differences in: the Ru-S bond lengths (~0.01 Å), the Ru-Cl-Ru angles (< 2 degrees), the Ru-S-
C(propyl) vs. the Ru-S-C(ethyl) angles. (< 2 degrees); the cis-S-Ru-S angles are 94.44 or 95.61◦
and there are no Ru-Ru bonds. The Ru-μ-Cl bond lengths in 3 and 4 are up to 0.1 Å longer than
the trans Ru-Cl bonds; these RuIII bonds are up to 0.1 Å shorter than the RuII-Cl bonds in
complexes 1 and 2. The structural data for 3 and 4 may be compared with those of another
III
Ru2 (μ-Cl)2 species Ru2Cl2(PPh3)2(μ-Cl)2(μ-salhn), H2salhn being a tetradentate N2O2 donor
Schiff base with two dissociable phenolic protons [22]; here, the terminal Ru-Cl bonds are 2.320
and 2.341 Å, and the longer Ru-μ-Cl bonds are in the range 2.369 to 2.428 Å, similar values and
trends to those found in 3 and 4.
X-ray quality crystals of complexes 5 and 6 were not obtained, but their elemental values
analyses and UV-Vis data (similar to those of 3 and 4) support their analogous formulations.
The solid-state magnetic susceptibilities of all four complexes were 3.0 to 3.8 ( 0.1) B. M. per
Ru, consistent with a single, unpaired electron, at none-interacting RuIII centres. No conductivity
was observed for these complexes in CH2Cl2 solution, and the complexes were insoluble in water.
Of note, some of the sulfoxides, synthesized by oxidation of the dithioethers (see Section 3.1),
form analogous bis(disulfoxide), chloro-bridged, dinuclear RuIII complexes that are water-soluble
and lead to a relatively high degree of DNA bonding [7]; this thesis work is currently being
arranged for publication.
Also, of note, the suggested formulation of [RuCl3(EtSCH2CH2SEt)1.5]n suggested by Chatt et
al. was described as ‘probably at least binuclear’ with one chelating and one bridging disulphide
[2]; this contrasts with our quite different structure for the 1,3-bis(ethylthio)propane analogue
[RuCl2(BETP)]2(-Cl)2 (Fig. 4); both elemental analyses for the formulations are correct. The
different products could result from steric effects, just (CH2) 2 vs. (CH2 )3 groups, but a more likely
possibility is the difference in the solvent systems used in the syntheses: again, acidified EtOH by
our group, whereas Chatt’s group used just EtOH [2].
16

Table 3. Selected bond lengths (Å) and bond angles (º) for [RuCl2(BETP)]2(-Cl)2 and
[RuCl2(BPTP)]2(-Cl)2.
Bond or Angle
[RuCl2(BETP)]2(-Cl)2 3
2.3249(9),b 2.3496(9)c
2.3911(9), 2.4628(9)
2.3196(9), 2.3675(9)
1.812(3)-1.820(3)
84.14(3)-96.73(3)
172.07(3)-175.84(3)
99.98(16), 100.46(11)
113.1(2), 117.0(2)
110.1(2), 112.74(19)
110.16(12), 111.81(11)
107.79(12), 110.60(11)
95.86(3)
[RuCl2(BPTP)]2(-Cl)2
2.3200(12),b 2.3566(13)c
2.3842(12), 2.4591(12)
2.3306(13), 2.3561(13)
1.810(5)-1.851(5)
82.94(4)-97.50(4)
173.35(4)-175.94(4)
98.9(3), 101.0(3)
4
Ru-Cla
Ru-Cld
Ru-S
C-S
cis angles
trans angles
C-S-C
S-C-Ce
S-C-Cf
112.1(4), 117.2(4)
111.3(4), 112.2(4)
110.17(12), 112.74(19)
109.81(18), 110.79(18)
97.05(4)
Ru-S-Ce
Ru-S-Cf
Ru-Cl-Ru
S-Ru-S
94.44(4)
95.61(5)
b
c
d
e
f
a Terminal Cl. Trans to Cl. Trans to S. Bridging Cl. Backbone C-atoms. End substituents.
17

Fig. 4. An ORTEP drawing of [RuCl2(BETP)]2(-Cl)2 (3) with 50 % probability thermal ellipsoids
shown; H-atoms are omitted for clarity.
18

Fig. 5. An ORTEP drawing of [RuCl2(BPTP)]2(-Cl)2 (4) with 50 % probability thermal
ellipsoids shown. The H-atoms are omitted for clarity.
4. Conclusions
Nine new, and two known, dithioethers of the type RS(CH2)xSR, where x = 2 or 3, and R is an
alkyl or aryl chain, are reported. Their reactions with RuCl3·3H2O generate either trans-
RuCl2(dithioether)2 or [RuCl2(RS(CH2)xSR)]2(-Cl)2 complexes, with both types being
characterized crystallographically. This current paper clarifies uncertainties in structures of Ru-
thioether complexes, and forms the basis of studies on the related sulfoxide systems. Further
studies (to be published) show that the dithioethers can be oxidized to the corresponding
disulfoxides that also form ruthenium complexes; such complexes are of the type known for their
biological properties, such as cell accumulation and toxicity, and DNA binding.
19

Acknowledgements
We thank the Natural Sciences and Engineering Research Council of Canada (NSERC, Grant
CRDP J 234014) and the Medical Research Council of Canada for financial support, and Colonial
Metals Inc. for the RuCl3٠3H2O.
Appendix A. Supplementary data
Supplementary material is Fig. S1. CCDC numbers 1895702-1895705 contain the
supplementary crystallographic data for complexes 3, 4, 1 and 2, respectively; these data can be
obtained free of charge from The Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associated with this article can
be found, in the online at https…………………..
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21

2NaOH
-2NaBr
Br(CH2)xBr + 2RSH
RS(CH2)xSR
RuCl 3H O
*
3
2
trans-RuCl2[RS(CH2)xSR]2
or
{[RuCl2[RS(CH2)xSR]2}(u-Cl)2
X = 2 or 3 ; R = alkyl, or Ph, or cyclohexyl
Highlights:
Syntheses of dithioethers, and their chloro -Ru(II and III) complexes
X-ray structures
22